Evidence map›Paper›PMID 30739015›Full record

ArticleiScience2019

Deacetylation Inhibition Reverses PABPN1-Dependent Muscle Wasting.

Cyriel S Olie, Muhammad Riaz, Rebecca Konietzny, Philip D Charles, Adan Pinto-Fernandez, Szymon M Kiełbasa, A Aartsma-Rus, Jelle J Goeman, Benedikt M Kessler, Vered Raz

Open access · goldAbstract read
In one paragraph

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Mouse models for muscular dystrophies: an overview.Disease models & mechanisms · 2020
    Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Cyriel S OlieDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Muhammad RiazDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Rebecca KonietznyTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Philip D CharlesTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Adan Pinto-FernandezTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Szymon M KiełbasaMedical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
A Aartsma-RusDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Jelle J GoemanMedical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Benedikt M KesslerTarget Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK.
Vered RazDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: v.raz@lumc.nl.
Leiden University Medical Center · NLUniversity of Oxford · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reduced poly(A)-binding protein nuclear 1 (PABPN1) levels cause aging-associated muscle wasting. PABPN1 is a multifunctional regulator of mRNA processing. To elucidate the molecular mechanisms causing PABPN1-mediated muscle wasting, we compared the transcriptome with the proteome in mouse muscles expressing short hairpin RNA to PABPN1 (shPab). We found greater variations in the proteome than in mRNA expression profiles. Protein accumulation in the shPab proteome was concomitant with reduced proteasomal activity. Notably, protein acetylation appeared to be decreased in shPab versus control proteomes (63%). Acetylome profiling in shPab muscles revealed prominent peptide deacetylation associated with elevated sirtuin-1 (SIRT1) deacetylase. We show that SIRT1 mRNA levels are controlled by PABPN1 via alternative polyadenylation site utilization. Most importantly, SIRT1 deacetylase inhibition by sirtinol increased PABPN1 levels and reversed muscle wasting. We suggest that perturbation of a multifactorial regulatory loop involving PABPN1 and SIRT1 plays an imperative role in aging-associated muscle wasting. VIDEO ABSTRACT.

Indexed as

Biological SciencesMolecular BiologyPhysiology

Identifiers

PMID30739015
PMCPMC6370712
OpenAlexW2911383041

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.